Gene specific repair studies in fibroblasts from a highly breast cancer prone Li-Fraumeni kindred have proven that there is a significant defect in gene-specific DNA repair in active and inactive genomic se Gene-specific quences. In addition, abnormal binding of the mutant p53 protein to the ERCC3 repair protein product has also been observed. These findings support the notion that defective DNA repair may be associated with heritable breast cancer but does not address the issue of sporadically occurring cancers. To address the question in sporadically occurring tumors, we have selected three breast cell lines to study: a normal human mammary epithelial cell (HMEC), the well studied hormone dependent MCF-7 cell line, and the hormone independent MDA-MB-468 cell lines. Our preliminary results suggest that both breast cancer cell lines are hypersensitive to ultraviolet light, hydrogen peroxide, and 4NQO. In contrast, the normal HMECs have sensitivity levels comparable to normal cell lines. In addition repair studies in bulk DNA reveal a defect in the processing and repair of UV-induced cyclobutane pyrimidine dimers. A singular preliminary gene-specific repair experiment performed on the tumor cell lines only suggests that repair at the gene level is also defective.